NM_080860.4:c.*53C>T

Variant names:

• chr21-42472765-G-A
• rs1043807
• NM_080860.4:c.*53C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080860.4(RSPH1):​c.*53C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 1,405,072 control chromosomes in the GnomAD database, including 6,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (615 hom., cov: 33)
  • Exomes 𝑓: 0.093 (6258 hom.)
• Consequence: RSPH1 NM_080860.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.124
• Publications: 12 publications found

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

RSPH1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 24

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-42472765-G-A is Benign according to our data. Variant chr21-42472765-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080860.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH1	NM_080860.4	MANE Select	c.*53C>T		3_prime_UTR	Exon 9 of 9	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.*53C>T		3_prime_UTR	Exon 8 of 8	NP_001273435.1	Q8WYR4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH1	ENST00000291536.8	TSL:1 MANE Select	c.*53C>T		3_prime_UTR	Exon 9 of 9	ENSP00000291536.3	Q8WYR4-1
	RSPH1	ENST00000856519.1		c.*53C>T		3_prime_UTR	Exon 8 of 8	ENSP00000526578.1
	RSPH1	ENST00000398352.3	TSL:5	c.*53C>T		3_prime_UTR	Exon 8 of 8	ENSP00000381395.3	Q8WYR4-2

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11222 AN: 152000 Hom.: 613 Cov.: 33

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0930 AC: 116536 AN: 1252954 Hom.: 6258 Cov.: 17 AF XY: 0.0966 AC XY: 61254 AN XY: 634348

African (AFR) AF: 0.0189 AC: 543 AN: 28796

American (AMR) AF: 0.0761 AC: 3188 AN: 41888

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3034 AN: 24458

East Asian (EAS) AF: 0.0776 AC: 2995 AN: 38614

South Asian (SAS) AF: 0.164 AC: 13116 AN: 80064

European-Finnish (FIN) AF: 0.0752 AC: 3989 AN: 53052

Middle Eastern (MID) AF: 0.204 AC: 1086 AN: 5318

European-Non Finnish (NFE) AF: 0.0900 AC: 83461 AN: 927544

Other (OTH) AF: 0.0963 AC: 5124 AN: 53220

GnomAD4 genome AF: 0.0738 AC: 11233 AN: 152118 Hom.: 615 Cov.: 33 AF XY: 0.0749 AC XY: 5570 AN XY: 74374

African (AFR) AF: 0.0199 AC: 828 AN: 41504

American (AMR) AF: 0.0871 AC: 1329 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3470

East Asian (EAS) AF: 0.0609 AC: 316 AN: 5188

South Asian (SAS) AF: 0.156 AC: 750 AN: 4814

European-Finnish (FIN) AF: 0.0784 AC: 828 AN: 10562

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0933 AC: 6347 AN: 67998

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0834 Hom.: 558

Bravo AF: 0.0723

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.37
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1043807; hg19: chr21-43892875; COSMIC: COSV107338674;